The CD4 Versus CD8 T Cell Fate Decision: A Multiomics-Informed Perspective.

The choice of developing thymocytes to become CD8+ cytotoxic or CD4+ helper T cells has been intensely studied, but many of the underlying mechanisms remain to be elucidated. Recent multiomics approaches have provided much higher resolution analysis of gene expression in developing thymocytes than was previously achievable, thereby offering a fresh perspective on this question. Focusing on our recent studies using CITE-seq (cellular indexing of transcriptomes and epitopes) analyses of mouse thymocytes, we present a detailed timeline of RNA and protein expression changes during CD8 versus CD4 T cell differentiation.

Single-cell multiomic analysis of thymocyte development reveals drivers of CD4 T cell and CD8 T cell lineage commitment.

The development of CD4 T cells and CD8 T cells in the thymus is critical to adaptive immunity and is widely studied as a model of lineage commitment. Recognition of self-peptide major histocompatibility complex (MHC) class I or II by the T cell antigen receptor (TCR) determines the CD8 or CD4 T cell lineage choice, respectively, but how distinct TCR signals drive transcriptional programs of lineage commitment remains largely unknown. Here we applied CITE-seq to measure RNA and surface proteins in thymocytes from wild-type and T cell lineage-restricted mice to generate a comprehensive timeline of cell states for each T cell lineage.

ECM-integrin signalling instructs cellular position sensing to pattern the early mouse embryo.

Development entails patterned emergence of diverse cell types within the embryo. In mammals, cells positioned inside the embryo give rise to the inner cell mass (ICM), which eventually forms the embryo itself. Yet, the molecular basis of how these cells recognise their 'inside' position to instruct their fate is unknown.

Coordination of Cell Polarity, Mechanics and Fate in Tissue Self-organization.

Self-organization guides robust, spatiotemporally ordered formation of complex tissues and ultimately whole organisms. While products of gene expression serve as building blocks of living matter, how these interact to give rise to tissues of distinct patterns and function remains a central question in biology. Tissue self-organization relies on dynamic interactions between constituents spanning a range of spatiotemporal scales with tuneable chemical and mechanical parameters.